The overall objective of this project is to develop an animal model for the study of AIDS-associated neoplasms such as Kaposi's sarcoma (KS). By understanding this animal model, we will be able to define the underlying mechanisms of etiology and to formulate therapeutic approaches for the treatment of these neoplasms. We intend to demonstrate that the tat gene of the human immunodeficiency virus (HIV) is responsible for the development of KS by utilizing transgenic mice which contain and express the HIV tat gee. Since there is no evidence for a direct role of HIV in the development of KS at present, this model will help to clarify the significant association between HIV infection and the development of KS. To understand the role of HIV in KS, this research project will attempt to define the molecular mechanisms of how tat induces KS in this transgenic animal model. The hypothesis is that potent viral transactivators, such as the product of the tat gene, have the ability to interact with the perturb the expression of cellular genes leading to a variety of disease states such as cell proliferation. In our transgenic model, we will dissect out the step-by-step events beginning with expression of the tat gene and culminating in the development of KS-like lesions. Biochemical and biological assays have been developed to help sort out events following expression of the tat gene, and further characterization of the actual proliferating cells using cell marker analysis will help our understanding of this confusing neoplasm which occurs in a high percentage of HIV-infected individuals.